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Gene Review

M6PR  -  mannose-6-phosphate receptor (cation...

Bos taurus

Synonyms: CD-MPR, CDMPR
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Disease relevance of M6PR

  • A recombinant baculovirus containing the cDNA for the full-length bovine cation-dependent mannose 6-phosphate receptor (CD-MPR) was generated by homologous recombination [1].

High impact information on M6PR


Biological context of M6PR

  • The structural requirements for oligomerization and the generation of a functional mannose 6-phosphate (Man-6-P) binding site of the cation-dependent mannose 6-phosphate receptor (CD-MPR) were analyzed [7].
  • We have studied the expression of the IGF-II/M6P receptor in fetal bovine tissues from 5 through 36 weeks' gestation [8].
  • The bovine cation-dependent mannose 6-phosphate receptor (CD-MPR) contains five potential N-linked glycosylation sites, four of which are utilized [9].

Anatomical context of M6PR

  • Ligand blot analysis using bovine testes beta-galactosidase showed that the monomeric form of the CD-MPR from bovine liver and testes is capable of binding Man-6-P [7].
  • Chemical cross-linking studies on affinity-purified CD-MPR and on solubilized membranes containing the receptor indicate that the CD-MPR exists as a homodimer [7].
  • We have developed a method for the isolation of the subcellular organelles from bovine liver which are enriched in the cation-independent mannose 6-phosphate receptor (CI-MPR) and the cation-dependent mannose 6-phosphate receptor (CD-MPR) [4].
  • Immunostaining of the tissues showed that both receptors localize to hepatocytes at all the ages and, additionally, the CD-MPR was reactive in megakaryocytes at early stages [10].
  • CI-MPR expression decreases progressively from 18-day fetuses to adults, whereas the CD-MPR showed a transient decrease in newborn and at the 5th day after birth [10].

Associations of M6PR with chemical compounds

  • A series of chemically synthesized oligomannosides that contain mannose 6-phosphate residues were utilized as inhibitors of the binding of beta-galactosidase to high (CI-MPR, 215 kDa) and low (CD-MPR, 41-46 kDa) molecular mass mannose 6-phosphate receptor from bovine testes in order to probe the specificity of each receptor [11].
  • Mammalian tissues express both cation-dependent (CD-MPR) and cation-independent (CI-MPR) mannose-6-phosphate receptors, which mediate the targeting of acid hydrolases to lysosomes [10].

Physical interactions of M6PR

  • Although the receptors exhibited similar relative specificities for phosphomonoesters, phosphodiesters did not inhibit binding of ligand to CD-MPR and only weakly inhibited binding to CI-MPR [11].

Other interactions of M6PR


Analytical, diagnostic and therapeutic context of M6PR

  • We have analyzed this interaction between the Golgi-restricted AP1 complex and the plasma membrane-restricted AP2 complex with the MPR46 tail in vitro by using a biosensor [5].
  • Chicken IgY antibodies specifically recognized the human and bovine 270-kDa M6P/IGFII-R but not the 46-kDa M6P-R, as documented by immunoprecipitation and immunobloting [13].
  • Immunoblotting was performed with anti-bovine IGF-II/M6P receptor antiserum [8].
  • To evaluate the function of these oligosaccharides, site-directed mutagenesis was used to generate glycosylation-deficient CD-MPR mutants lacking various potential glycosylation sites [9].
  • In conclusion, the full-length CD-MPR produced in P. pastoris is structurally and functionally suitable for crystallization studies [14].


  1. Expression and characterization of functional bovine cation-dependent mannose 6-phosphate receptors in baculovirus-infected insect cells. Dahms, N.M., Brzycki-Wessell, M.A. Arch. Biochem. Biophys. (1995) [Pubmed]
  2. 46 kd mannose 6-phosphate receptor: cloning, expression, and homology to the 215 kd mannose 6-phosphate receptor. Dahms, N.M., Lobel, P., Breitmeyer, J., Chirgwin, J.M., Kornfeld, S. Cell (1987) [Pubmed]
  3. A determinant in the cytoplasmic tail of the cation-dependent mannose 6-phosphate receptor prevents trafficking to lysosomes. Rohrer, J., Schweizer, A., Johnson, K.F., Kornfeld, S. J. Cell Biol. (1995) [Pubmed]
  4. Isolation and characterization of membranes from bovine liver which are highly enriched in mannose 6-phosphate receptors. Messner, D.J., Griffiths, G., Kornfeld, S. J. Cell Biol. (1989) [Pubmed]
  5. The 46-kDa mannose 6-phosphate receptor contains multiple binding sites for clathrin adaptors. Höning, S., Sosa, M., Hille-Rehfeld, A., von Figura, K. J. Biol. Chem. (1997) [Pubmed]
  6. In vitro binding of plasma membrane-coated vesicle adaptors to the cytoplasmic domain of lysosomal acid phosphatase. Sosa, M.A., Schmidt, B., von Figura, K., Hille-Rehfeld, A. J. Biol. Chem. (1993) [Pubmed]
  7. The cation-dependent mannose 6-phosphate receptor. Structural requirements for mannose 6-phosphate binding and oligomerization. Dahms, N.M., Kornfeld, S. J. Biol. Chem. (1989) [Pubmed]
  8. The insulin-like growth factor-II/mannose-6-phosphate receptor is present in fetal bovine tissues throughout gestation. Pfuender, M., Sauerwein, H., Funk, B., Kessler, U., Barenton, B., Schwarz, H.P., Hoeflich, A., Kiess, W. Domest. Anim. Endocrinol. (1995) [Pubmed]
  9. Site-directed removal of N-glycosylation sites in the bovine cation-dependent mannose 6-phosphate receptor: effects on ligand binding, intracellular targetting and association with binding immunoglobulin protein. Zhang, Y., Dahms, N.M. Biochem. J. (1993) [Pubmed]
  10. Expression and binding properties of the two mannose-6-phosphate receptors differ during perinatal development in rat liver. Romano, P.S., López, A.C., Mariani, M.L., Sartor, T., Belmonte, S.A., Sosa, M.A. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  11. The binding specificity of high and low molecular weight phosphomannosyl receptors from bovine testes. Inhibition studies with chemically synthesized 6-O-phosphorylated oligomannosides. Distler, J.J., Guo, J.F., Jourdian, G.W., Srivastava, O.P., Hindsgaul, O. J. Biol. Chem. (1991) [Pubmed]
  12. Identification and characterization of insulin-like growth factor I (IGF-I) and IGF-II/mannose-6-phosphate (IGF-II/M6P) receptors in bovine adrenal cells. Weber, M.M., Kiess, W., Beikler, T., Simmler, P., Reichel, M., Adelmann, B., Kessler, U., Engelhardt, D. Eur. J. Endocrinol. (1994) [Pubmed]
  13. High-affinity antibodies from hen's-egg yolks against human mannose-6-phosphate/insulin-like growth-factor-II receptor (M6P/IGFII-R): characterization and potential use in clinical cancer studies. Lemamy, G.J., Roger, P., Mani, J.C., Robert, M., Rochefort, H., Brouillet, J.P. Int. J. Cancer (1999) [Pubmed]
  14. Biochemical and functional properties of the full-length cation-dependent mannose 6-phosphate receptor expressed in Pichia pastoris. Reddy, S.T., Kumar, S.N., Haas, A.L., Dahms, N.M. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
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